Clinical Trial: Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Observational

Official Title: Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage

Brief Summary: Recently, the occurrence and potential impact of pituitary dysfunction after aSAH has gained increasing interest. Several studies have demonstrated pituitary dysfunction after SAH suggesting that pituitary dysfunction may be a contributing factor for residual symptoms after SAH. This is an observational multicentric study aimed to test the prevalence of thyroid abnormalities, other neuroendocrinological dysfunction and their influence on outcome of patients affected by aSAH.

Detailed Summary:

The incidence of aneurysmal subarachnoid hemorrhage (aSAH) varies between 6 to 10/100,000 subjects per year and it is a major cause of death and disability. The mortality rate ranges from 40 to 50%, and those who do survive SAH have high rates of functional limitations that could lead to impaired quality of life, including fatigue, depression, and loss of motivation.

Because aSAH affects patients in their most productive years of life, the disease has important social, and economic implications, and early prediction of long-term outcome is based on multiple factors including the primary injury secondary insults as well as neurorehabilitation interventions.

Recently, the occurrence and potential impact of pituitary dysfunction after aSAH has gained increasing interest. Several studies have demonstrated pituitary dysfunction after SAH suggesting that pituitary dysfunction may be a contributing factor for residual symptoms after SAH. However, questions remain about the real prevalence and impact of such dysfunction on patients' outcome both in the acute and chronic phase after these events.

In two recent metanalysis, the prevalence of total pituitary dysfunction was found with pooled frequencies of 0.31 (95% confidence interval CI: 0.22-0.43) [Can et a.] and 49.3.0% (95% CI 41.6%-56.9%) [Robba et al] during the acute phase (< 6 months from aSAH) and decreasing in the chronic phase to 0.25 (95% CI: 0.16-0.36) [Can et al.] and 25.6% (95% CI 18.0%-35.1%) [Robba et al]. However, the authors found high heterogenicity and different results between the available literature; many differences were found in the in the choice of time of pituitary function assessment and SAH, of diagnostic criteria and units of measurement used to establish the diagnosis of hypopituitarism after SAH. Sponsor: Dr. Rita Bertuetti

Current Primary Outcome:

• Incidence of thyroid disfunction [ Time Frame: At 2 weeks after aSAH ]
  Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
• Incidence of thyroid disfunction [ Time Frame: 3 months after aSAH ]
  Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
• Incidence of thyroid disfunction [ Time Frame: 6 months after aSAH ]
  Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
• Incidence of thyroid disfunction [ Time Frame: 12 months after aSAH ]
  Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Incidence of pituitary- sexual hormones disfunction [ Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months. ]
  serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (in women), testosterone (in men), sex hormone-binding globulin (SHBG).
• Survival [ Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months ]
  Modified Ranking Scale
• Incidence of pituitary-adrenal axis disfunction [ Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months. ]
  Serum levels of adrenocortico-tropic hormone (ACTH), cortisol, Na, K; serum and urine osmolality. Adrenal function will be evaluated through ACTH-stimulation testing with injection of 250 mcg of ACTH, and a peak of cortisol <500 nmol/l will be considered pathologic. Adrenal or GH insufficiency will be evaluated by insulin tolerance testing (ITT), and peak response of more than 3ng/ml for GH and and 500 nmol/l for cortisol will be considered as normal.
• Incidence of growth hormone insufficiency [ Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months ]
  serum levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Adrenal or GH insufficiency will be evaluated by insulin tolerance testing (ITT), and peak response of more than 3ng/ml for GH and and 500 nmol/l for cortisol will be considered as normal.
• Incidence of language disorders [ Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months ]

  Neuropsychological examination focused on verbal comprehension will be evaluated through the application of Token Test .

  Incidence of impaired scoring will be correlated to incidence of altered hormone levels detected in the blood.

• Incidence of memory disorders [ Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months ]

  Verbal and visual short term and working memory visuospatial construction and figural memory will be performed through Rey Osterrieth Complex figure test.

  Incidence of impaired scoring will be correlated to incidence of altered hormone levels detected in the blood.

• Incidence of attention disorders [ Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months ]

  Psychomotor speed attention and concentration will be assessed through Trail Making Test.

  Incidence of impaired scoring will be correlated to incidence of altered hormone levels detected in the blood.

Original Secondary Outcome: Same as current

Information By: Cambridge University Hospitals NHS Foundation Trust

Dates:
Date Received: September 6, 2016
Date Started: January 2017
Date Completion: January 2018
Last Updated: September 23, 2016
Last Verified: September 2016